Two-Color Near-Infrared Fluorescence Guided Surgery Tools Enabling Simultaneous Cancer Margin and Nerve Visualization during Head and Neck Squamous Cell Carcinoma Resection
双色近红外荧光引导手术工具可在头颈鳞状细胞癌切除过程中同时实现癌症边缘和神经可视化
基本信息
- 批准号:10603689
- 负责人:
- 金额:$ 38.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-23 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:Adipose tissueAnatomyBiological SciencesBlood VesselsCancer ControlClinicalClinical MedicineClinical TrialsCollaborationsColorComplexContrast MediaDetectionDevelopmentDoseEnsureEpidermal Growth Factor ReceptorExcisionFaceFamily suidaeFasciaFluorescenceFluorescent ProbesFrequenciesGoalsHead CancerHead and Neck CancerHead and Neck Squamous Cell CarcinomaHead and neck structureHourImageImage-Guided SurgeryIncidenceInjectionsIntegrinsLeadLengthLettersLifeLightMalignant NeoplasmsMetalloproteasesModelingMuscleNeck CancerNerveNormal tissue morphologyOperative Surgical ProceduresOutcomePalpationPatientsPeptidesPerformancePersistent painPharmacologyPhasePlaguePreclinical TestingProceduresQuality of lifeRattusRecurrent Laryngeal NerveReporterResolutionRodentSignal TransductionSiteSpinalStructureStructure of phrenic nerveSurgeonSurgical marginsSurvival RateSystemTechnologyTechnology AssessmentTimeTissuesVagus nerve structureVertebral columnVisualizationWorkchromophoreclinical imagingclinical translationcomorbiditydesignexperiencefallsfluorescence imagingfluorescence-guided surgeryfluorophorehead and neck cancer patientimaging capabilitiesimaging probeimaging systemimprovedinnovationintravenous administrationloss of functionmanufacturing testmouse modelnerve damageneurotransmissionnovelpreclinical developmentpreservationsmall moleculespared nervesurgery outcometargeted imagingtooltumoruptake
项目摘要
PROJECT SUMMARY
Head and neck squamous cell carcinoma (HNSCC) is the sixth highest incidence cancer worldwide, with
>650,000 cases annually. Surgery is a primary treatment option for HNSCC, during which surgeons face two
main goals: 1) complete cancer resection and 2) preservation of normal tissue structures such as muscle, blood
vessels, and nerves to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where
complete cancer resection is often limited by efforts to preserve normal tissue and reduce life altering
comorbidities. In fact, positive surgical margins are found in 20-30% of patients, and nerve damage represents
a major surgical comorbidity, with 5-30% of patients experiencing lasting pain or loss of function. Currently, no
technology exists to enhance intraoperative cancer and nerve recognition. Thus, technology to provide
direct visualization of cancer margins and nerves simultaneously in real time would greatly improve surgical
outcomes and reduce comorbidities for HNSCC patients. Fluorescence Guided Surgery (FGS) has successfully
integrated into clinical medicine, providing surgeons real-time visualization of important tissues and complex
anatomy. Using compact and high-resolution FGS imaging systems, which operate almost exclusively in the
near-infrared (NIR, 700-900 nm), surgeons can image targeted fluorescent probes with high contrast at up to
centimeter depths. NIR Nerve-specific and HNSCC-targeted probes under development would together provide
an integrated FGS tool for HNSCC resection. Several peptide-based FGS imaging probes have demonstrated
efficacy in identifying tumor margins and are currently in phase II and III clinical trials, including those targeting
epidermal growth factor receptor (EGFR), matrix metalloprotease (MMP), and integrins. We have developed
first-in-class NIR nerve-specific fluorescent small-molecule probes that demonstrate high nerve signal to all
background tissues (e.g., muscle, adipose, vasculature, fascia, etc.) following intravenous administration in
rodents and swine. Importantly, the tumor-targeting FGS probes utilize fluorescent reporters centered at 800-nm
wavelengths, while our nerve-specific probes fluoresce at 700-nm wavelengths, providing spectrally distinct
tissue detection and compatibility with existing two-color FGS systems. The combination of these two
promising technologies would provide a comprehensive, innovative solution to enhance cancer control
and nerve sparing during HNSCC resection. This study’s immediate milestones will include (1)
characterization of our lead NIR nerve-specific fluorophore for head and neck procedures, (2) quantification of
tumor- and nerve-specific FGS probe co-administration performance including cross-talk, and (3) assessment of
this technology using a clinical two-color FGS system. This work will result in the first comprehensive FGS tool
for cancer resection and nerve sparing during head and neck procedures. The proposed development will
provide important proof-of-concept for further development and partnership. In Phase II, the first two-color tumor
and nerve targeted FGS studies will be completed in patients undergoing HNSCC resection.
项目摘要
头颈部鳞状细胞癌(HNSCC)是世界上发病率第六高的癌症,
每年超过65万例。手术是HNSCC的主要治疗选择,在此期间,外科医生面临两个
主要目标:1)完全切除肿瘤; 2)保留正常组织结构,如肌肉、血液
血管和神经,以确保术后生活质量。不幸的是,这些目标不是协同的,
完整的癌症切除术通常受到保护正常组织和减少生命改变的努力的限制。
合并症。事实上,在20-30%的患者中发现了手术切缘阳性,神经损伤代表了
一种主要的外科并发症,5-30%的患者经历持续疼痛或功能丧失。当前没有任何
存在增强术中癌症和神经识别的技术。因此,技术提供
在真实的时间内同时直接可视化癌边缘和神经将极大地改善外科手术。
结果和减少HNSCC患者的合并症。荧光引导手术(FGS)已成功
集成到临床医学中,为外科医生提供重要组织和复杂组织的实时可视化
解剖学。使用紧凑和高分辨率的FGS成像系统,该系统几乎只在
近红外(NIR,700-900 nm),外科医生可以成像靶向荧光探针,具有高对比度,
厘米深。正在开发的NIR神经特异性和HNSCC靶向探针将共同提供
用于HNSCC切除的集成FGS工具。几种基于肽的FGS成像探针已被证明
目前正在进行II期和III期临床试验,包括那些靶向
表皮生长因子受体(EGFR)、基质金属蛋白酶(MMP)和整联蛋白。我们已经开发
一流的近红外神经特异性荧光小分子探针,可向所有人显示高神经信号
背景组织(例如,肌肉、脂肪、脉管系统、筋膜等)静脉给药后,
啮齿动物和猪。重要的是,肿瘤靶向FGS探针利用以800 nm为中心的荧光报告子
波长,而我们的神经特异性探针在700 nm波长处发出荧光,
组织检测和与现有双色FGS系统的兼容性。通过结合使用这两
有前途的技术将提供一个全面的,创新的解决方案,以加强癌症控制
和神经保留。本研究的近期里程碑包括(1)
我们的头部和颈部程序的主要NIR神经特异性荧光团的表征,(2)定量
肿瘤和神经特异性FGS探针共施用性能,包括串扰,和(3)评估
该技术使用临床双色FGS系统。这项工作将导致第一个全面的FGS工具
用于头颈部手术中的癌症切除和神经保留。拟议的发展将
为进一步发展和伙伴关系提供重要的概念验证。在第二阶段,第一个双色肿瘤
神经靶向FGS研究将在接受HNSCC切除术的患者中完成。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Connor William Barth其他文献
Connor William Barth的其他文献
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{{ truncateString('Connor William Barth', 18)}}的其他基金
Intraoperative Nerve Damage Assessment Using Nerve-Specific Fluorescence Guided Surgery
使用神经特异性荧光引导手术进行术中神经损伤评估
- 批准号:
10482087 - 财政年份:2022
- 资助金额:
$ 38.62万 - 项目类别:
Clinical Translation of Near Infrared Nerve-Specific Fluorophores for Nerve-sparing Prostatectomy
近红外神经特异性荧光团在保留神经的前列腺切除术中的临床转化
- 批准号:
10838010 - 财政年份:2022
- 资助金额:
$ 38.62万 - 项目类别:
Clinical Translation of Near Infrared Nerve-Specific Fluorophores for Nerve-sparing Prostatectomy
近红外神经特异性荧光团在保留神经的前列腺切除术中的临床转化
- 批准号:
10633513 - 财政年份:2022
- 资助金额:
$ 38.62万 - 项目类别:
Clinical Translation of Near Infrared Nerve-Specific Fluorophores for Nerve-sparing Prostatectomy
近红外神经特异性荧光团在保留神经的前列腺切除术中的临床转化
- 批准号:
10081607 - 财政年份:2021
- 资助金额:
$ 38.62万 - 项目类别:
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